Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 31, 2024
Abstract
The
patch
clamp
technique
is
a
fundamental
tool
for
investigating
ion
channel
dynamics
and
electrophysiological
properties.
This
study
proposes
the
first
artificial
intelligence
framework
characterizing
multiple
kinetics
of
whole‐cell
recordings.
integrates
machine
learning
anomaly
detection
deep
multi‐class
classification.
excludes
recordings
that
are
incompatible
with
behavior.
classification
combined
1D
convolutional
neural
network,
bidirectional
long
short‐term
memory,
an
attention
mechanism
to
capture
spatiotemporal
patterns
achieves
accuracy
97.58%
in
classifying
124
test
datasets
into
six
categories
based
on
kinetics.
utility
novel
demonstrated
two
applications:
Alzheimer's
disease
drug
screening
nanomatrix‐induced
neuronal
differentiation.
In
screening,
illustrates
inhibitory
effects
memantine
endogenous
channels,
antagonistic
interactions
among
potassium,
magnesium,
calcium
channels.
For
differentiation,
classifier
indicates
differentiation
conditions
sodium
potassium
channels
associated
action
potentials,
validating
functional
properties
differentiated
neurons
Parkinson's
treatment.
proposed
promising
enhancing
efficiency
analysis
research.
Aging and Disease,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
The
blood-brain
barrier
(BBB)
plays
a
critical
role
in
maintaining
ion
and
fluid
homeostasis,
essential
for
brain
metabolism
neuronal
function.
Regulation
of
nutrient,
water,
transport
across
the
BBB
is
tightly
controlled
by
specialized
transporters
channels
located
within
its
unique
cellular
components.
These
dynamic
processes
not
only
influence
BBB’s
structure
but
also
impact
vital
signaling
mechanisms,
optimal
Disruption
ion,
pH,
balance
at
associated
with
pathology
has
been
implicated
various
neurological
conditions,
including
stroke,
epilepsy,
trauma,
neurodegenerative
diseases
such
as
Alzheimer’s
disease
(AD).
However,
knowledge
gaps
exist
regarding
dysregulation
on
function
dementias.
Several
factors
contribute
to
this
gap:
complex
nature
these
historical
research
focus
mechanisms
technical
challenges
studying
in
vivo
models
lack
efficient
vitro
dementia
models.
This
review
provides
an
overview
current
roles
poses
specific
questions:
1)
How
are
expression
activity
key
altered
AD
vascular
(VaD);
2)
Do
changes
dysfunction
progression;
3)
Can
restoring
mitigate
improve
clinical
outcomes.
Addressing
will
provide
greater
insight
into
disorders.
Cellular and Molecular Neurobiology,
Год журнала:
2024,
Номер
44(1)
Опубликована: Июль 26, 2024
Abstract
Optogenetics,
a
revolutionary
technique
integrating
optical
and
genetic
methodologies,
offers
unparalleled
precision
in
spatial
targeting
temporal
resolution
for
cellular
control.
This
approach
enables
the
selective
manipulation
of
specific
neuronal
populations,
inducing
subtle
electrical
changes
that
significantly
impact
complex
neural
circuitry.
As
optogenetics
precisely
targets
modulates
activity,
it
holds
potential
significant
breakthroughs
understanding
potentially
altering
course
neurodegenerative
diseases,
characterized
by
loss
leading
to
functional
deficits
within
nervous
system.
The
integration
into
disease
research
has
advanced
field,
offering
new
insights
paving
way
innovative
treatment
strategies.
Its
application
clinical
settings,
although
still
nascent
stages,
suggests
promising
future
addressing
some
most
challenging
aspects
disorders.
In
this
review,
we
provide
comprehensive
overview
these
undertakings.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(10), С. 9022 - 9022
Опубликована: Май 19, 2023
Amyotrophic
lateral
sclerosis
(ALS)
is
manifested
as
skeletal
muscle
denervation,
loss
of
motor
neurons
and
finally
severe
respiratory
failure.
Mutations
RNA-binding
protein
FUS
are
one
the
common
genetic
reasons
ALS
accompanied
by
a
‘dying
back’
type
degeneration.
Using
fluorescent
approaches
microelectrode
recordings,
early
structural
functional
alterations
in
diaphragm
neuromuscular
junctions
(NMJs)
were
studied
mutant
mice
at
pre-onset
stage.
Lipid
peroxidation
decreased
staining
with
lipid
raft
marker
found
mice.
Despite
preservation
end-plate
structure,
immunolabeling
revealed
an
increase
levels
presynaptic
proteins,
SNAP-25
synapsin
1.
The
latter
can
restrain
Ca2+-dependent
synaptic
vesicle
mobilization.
Indeed,
neurotransmitter
release
upon
intense
nerve
stimulation
its
recovery
after
tetanus
compensatory
endocytosis
markedly
depressed
There
was
trend
to
attenuation
axonal
[Ca2+]in
20
Hz.
However,
no
changes
intraterminal
Ca2+
transient
response
low
frequency
or
quantal
content
synchrony
external
detected.
At
later
stage,
shrinking
fragmentation
end
plates
together
decrease
expression
disturbance
timing
occurred.
Overall,
suppression
exo–endocytosis
activity
probably
due
membrane
properties,
1
kinetics
could
be
sign
nascent
NMJ
pathology,
which
leads
contact
disorganization.
Antioxidants,
Год журнала:
2023,
Номер
12(4), С. 920 - 920
Опубликована: Апрель 13, 2023
Aging
is
a
complex
process
of
impaired
physiological
integrity
and
function,
associated
with
increased
risk
cardiovascular
disease,
diabetes,
neurodegeneration,
cancer.
The
cellular
environment
the
aging
brain
exhibits
perturbed
bioenergetics,
adaptive
neuroplasticity
flexibility,
abnormal
neuronal
network
activity,
dysregulated
Ca2+
homeostasis,
accumulation
oxidatively
modified
molecules
organelles,
clear
signs
inflammation.
These
changes
make
susceptible
to
age-related
diseases,
such
as
Alzheimer’s
Parkinson’s
diseases.
In
recent
years,
unprecedented
advances
have
been
made
in
study
aging,
especially
effects
herbal/natural
compounds
on
evolutionarily
conserved
genetic
pathways
biological
processes.
Here,
we
provide
comprehensive
review
discuss
molecular
mechanisms
underlying
therapeutic
properties
against
hallmarks
aging.
Molecules,
Год журнала:
2024,
Номер
29(19), С. 4724 - 4724
Опубликована: Окт. 6, 2024
Cognitive
impairment
(CI)
is
a
type
of
mental
health
disorder
that
mainly
affects
cognitive
abilities,
such
as
learning,
memory,
perception,
and
problem-solving.
Currently,
in
clinical
practice,
the
treatment
focuses
on
application
cholinesterase
inhibitors
NMDA
receptor
antagonists;
however,
there
no
specific
effective
drug
yet.
Procatechuic
acid
(PCA)
possesses
various
functions,
including
antibacterial,
antiasthmatic,
expectorant
effects.
In
recent
years,
it
has
received
growing
attention
domain.
Therefore,
by
summarizing
mechanisms
action
procatechuic
this
paper,
found
multiple
effects,
regulating
expression
neuroprotective
factors,
inhibiting
cell
apoptosis,
promoting
autophagy-lysosome
pathway,
suppressing
oxidative
stress
damage,
inflammatory
responses,
improving
synaptic
plasticity
dysfunction,
Aβ
deposition,
reducing
APP
hydrolysis,
enhancing
cholinergic
system,
excitotoxicity
neuronal
cells.
The
involved
signaling
pathways
include
activating
Pi3K-akt-mTor
JNK,
P38
MAPK,
P38-ERK-JNK,
SIRT1,
NF-κB/p53,
etc.
This
paper
aims
to
present
latest
progress
research
acid,
aspects
its
chemical
properties,
sources,
pharmacokinetics,
for
treating
neurodegenerative
diseases.
The Neuroscientist,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 11, 2025
Microglia
serve
as
vital
innate
immune
cells
in
the
central
nervous
system,
playing
crucial
roles
generation
and
development
of
brain
neurons,
well
mediating
a
series
inflammatory
responses.
The
morphologic
transitions
microglia
are
closely
linked
to
their
function.
With
advent
single-cell
sequencing
technology,
diversity
microglial
subtypes
is
increasingly
recognized.
intricate
interactions
between
neuronal
networks
have
significant
implications
for
psychiatric
disorders
neurodegenerative
diseases.
A
deeper
investigation
neurologic
diseases
such
Alzheimer
disease,
depression,
epilepsy
can
provide
valuable
insights
understanding
pathogenesis
exploring
novel
therapeutic
strategies,
thereby
addressing
issues
related
system
disorders.
Journal of Neurochemistry,
Год журнала:
2025,
Номер
169(4)
Опубликована: Апрель 1, 2025
Lumbar
disc
herniation
(LDH)
is
a
common
chronic
orthopedic
condition
characterized
by
the
protrusion
of
nucleus
pulposus
tissue,
leading
to
low
back
and
leg
pain.
Its
pathophysiology
remains
poorly
understood.
The
aim
this
study
was
investigate
whether
demethylase
Fat
mass
obesity-associated
protein
(FTO)
mediates
local
translation
P2X3
receptors
(P2X3R)
in
rat
model
LDH.
effect
process
on
excitability
dorsal
root
ganglion
(DRG)
cells
also
examined,
which
may
elucidate
peripheral
molecular
mechanisms
underlying
specific
pain
sensitivity
LDH
models
were
established
male
Sprague-Dawley
rats.
Behavioral
tests
assessed
mechanical
thermal
thresholds
motor
function.
expression
P2X3R
FTO
DRG
investigated
RT-qPCR,
Western
blot,
immunofluorescence.
knocked
down,
methylation
examined
MeRIP
validate
their
roles.
IL-1β
IL-6
levels
quantified
ELISA.
Protein
interactions
predicted
using
AutoDock,
neuronal
patch
clamp
recordings.
Compared
with
Sham
group,
group
showed
reduction
threshold
hind
limbs.
There
no
significant
differences
increased
group.
DRG,
localized
mainly
cell
membrane
colocalized
NeuN.
Intrathecal
injection
P2X3R-siRNA
FTO-siRNA
effective
increasing
thresholds,
reducing
FTO,
decreasing
neurons,
IL-6.
RNA
Methylation
Immunoprecipitation
(MeRIP)
analysis
revealed
reduced
m6A
modification
mRNA
AutoDock
hydrogen
bond
between
P2X3R.
These
findings
suggest
that
regulates
DRG.
This
influences
contributes
LDH-induced
hyperalgesia.
Pharmaceutical Development and Technology,
Год журнала:
2025,
Номер
unknown, С. 1 - 17
Опубликована: Апрель 3, 2025
Self
nano-emulsifying
drug
delivery
system
(SNEDDS)
has
been
widely
used
to
enhance
dissolution
and
bioavailability
of
glibenclamide
(GB).
In
addition,
black
seed
oil,
containing
bioactive
thymoquinone
(TQ),
showed
promising
antihyperglycemic
effect.
Therefore,
this
work
aims
design
solid
SNEDDS
formulation
composed
Black
oil
loaded
with
GB
its
activity.
Different
formulations
were
prepared
characterized
for
miscibility,
dispersibility,
droplet
size,
zeta
potential,
in-vitro
dissolution.
Moreover,
antidiabetic
activity
against
pure
was
evaluated
using
streptozotocin-induced
diabetic
rat
model.
The
selected
liquid
(F7)
consisted
Kolliphor
EL:
Caproyl
90:
BSO
that
produced
nanoemulsion
particles
(24.9
±
0.2nm).
solidified
from
F7,
the
(S4)
as
optimum
TQ
had
a
DE%
value
73.16
0.59
70.9%,
respectively.
Overall,
both
GB-SNEDDS
significantly
reduced
blood
glucose
levels
compared
control
group.
showing
superior
efficacy
(67%
reduction,
p
=
5.5
×
10-5)
(52%
1.5
10-4).
GB-SNEDD
significant
(p
0.0363)
reducing
action
on
Present
results
boosted
oral
hypoglycemic
drugs.
This
could
open
new
avenues
natural
agent
while
preparing
formulation.
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 31, 2025
Abstract
First
identified
40
years
ago
in
cardiac
myocytes,
ATP‐sensitive
potassium
(K
ATP
)
channels
have
been
found
almost
all
excitable
tissues,
with
paradigmatic
inhibition
by
and
activation
ADP
underlying
their
physiological
role
coupling
cellular
metabolism
to
electrical
activity.
Cloning
of
the
genes,
30
ago,
revealed
unique
assembly
as
four
Kir6.x
pore‐forming
subunit
proteins
sulfonylurea
receptor
(SURx)
has
since
led
discovery
a
spectrum
monogenic
diseases
resulting
from
gain‐
(GOF)
or
loss‐of‐function
(LOF)
mutations,
turn
leading
recognition
novel
roles
pathophysiological
consequences
throughout
body.
With
this
perspective,
lecture
represents
personal
view
these
discoveries
potential
for
future
insights.
image
